Sex-specific effect of Pirin gene on bone mineral density in a cohort of 4000 Chinese

Nelson L S Tang, Chen Di Liao, Jasmine K L Ching, Eddie W C Suen, Iris H S Chan, Eric Orwoll, Suzanne C. Ho, Frank W K Chan, Anthony W L Kwok, Timothy Kwok, Jean Woo, Ping Chung Leung

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Background: Osteoporosis is a common condition among elderly. Genetic mapping studies repeatedly located the distal short arms of X-chromosome as the quantitative trait loci (QTL) for BMD in mice. Fine mapping of a syntenic segment on Xp22 in a Caucasian female population suggested a moderate association between lumbar spine (LS) BMD and 2 intronic SNPs in the Pirin (PIR) gene, which encodes an iron-binding nuclear protein. This study aimed to examine genetic variations in the PIR gene by a comprehensive tagging method and its sex-specific effects on BMD and osteoporotic risk. Methods: Two thousand men and 2000 women aged 65 or above were recruited from the community. BMDs at the LS, femoral neck, total hip and whole body were measured and followed up at 4-year. Genotyping was performed for tagSNPs of PIR gene including adjacent regions, and the PIR haplotypes were inferred using PHASE program. Results: Analysis by linear regression showed a significant association between SNP rs5935970 and LS-BMD, while haplotype T-T-A was significantly associated with BMD of all measured sites. However, none of such associations were found in men. Linear Mixed Model also confirmed the same sex-specific and site-specific effect for longitudinal BMD changes. Conclusion: In addition to confirming the association between BMDs and the PIR gene, we also revealed that this finding is sex-specific, possibly due to an X-linked effect. This study demonstrated the importance of considering sex and genetic interactions in studies of disease predisposition and complex traits.

Original languageEnglish (US)
Pages (from-to)543-550
Number of pages8
JournalBone
Volume46
Issue number2
DOIs
StatePublished - Feb 2010

Fingerprint

Bone Density
Spine
Haplotypes
Genes
Single Nucleotide Polymorphism
Linear Models
Iron-Binding Proteins
Quantitative Trait Loci
Femur Neck
X Chromosome
Nuclear Proteins
Osteoporosis
Hip
Population

Keywords

  • Bone mineral density
  • PIR
  • Pirin
  • Sex-specific effect
  • Single nucleotide polymorphism

ASJC Scopus subject areas

  • Physiology
  • Endocrinology, Diabetes and Metabolism
  • Histology

Cite this

Tang, N. L. S., Liao, C. D., Ching, J. K. L., Suen, E. W. C., Chan, I. H. S., Orwoll, E., ... Leung, P. C. (2010). Sex-specific effect of Pirin gene on bone mineral density in a cohort of 4000 Chinese. Bone, 46(2), 543-550. https://doi.org/10.1016/j.bone.2009.09.012

Sex-specific effect of Pirin gene on bone mineral density in a cohort of 4000 Chinese. / Tang, Nelson L S; Liao, Chen Di; Ching, Jasmine K L; Suen, Eddie W C; Chan, Iris H S; Orwoll, Eric; Ho, Suzanne C.; Chan, Frank W K; Kwok, Anthony W L; Kwok, Timothy; Woo, Jean; Leung, Ping Chung.

In: Bone, Vol. 46, No. 2, 02.2010, p. 543-550.

Research output: Contribution to journalArticle

Tang, NLS, Liao, CD, Ching, JKL, Suen, EWC, Chan, IHS, Orwoll, E, Ho, SC, Chan, FWK, Kwok, AWL, Kwok, T, Woo, J & Leung, PC 2010, 'Sex-specific effect of Pirin gene on bone mineral density in a cohort of 4000 Chinese', Bone, vol. 46, no. 2, pp. 543-550. https://doi.org/10.1016/j.bone.2009.09.012
Tang, Nelson L S ; Liao, Chen Di ; Ching, Jasmine K L ; Suen, Eddie W C ; Chan, Iris H S ; Orwoll, Eric ; Ho, Suzanne C. ; Chan, Frank W K ; Kwok, Anthony W L ; Kwok, Timothy ; Woo, Jean ; Leung, Ping Chung. / Sex-specific effect of Pirin gene on bone mineral density in a cohort of 4000 Chinese. In: Bone. 2010 ; Vol. 46, No. 2. pp. 543-550.
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abstract = "Background: Osteoporosis is a common condition among elderly. Genetic mapping studies repeatedly located the distal short arms of X-chromosome as the quantitative trait loci (QTL) for BMD in mice. Fine mapping of a syntenic segment on Xp22 in a Caucasian female population suggested a moderate association between lumbar spine (LS) BMD and 2 intronic SNPs in the Pirin (PIR) gene, which encodes an iron-binding nuclear protein. This study aimed to examine genetic variations in the PIR gene by a comprehensive tagging method and its sex-specific effects on BMD and osteoporotic risk. Methods: Two thousand men and 2000 women aged 65 or above were recruited from the community. BMDs at the LS, femoral neck, total hip and whole body were measured and followed up at 4-year. Genotyping was performed for tagSNPs of PIR gene including adjacent regions, and the PIR haplotypes were inferred using PHASE program. Results: Analysis by linear regression showed a significant association between SNP rs5935970 and LS-BMD, while haplotype T-T-A was significantly associated with BMD of all measured sites. However, none of such associations were found in men. Linear Mixed Model also confirmed the same sex-specific and site-specific effect for longitudinal BMD changes. Conclusion: In addition to confirming the association between BMDs and the PIR gene, we also revealed that this finding is sex-specific, possibly due to an X-linked effect. This study demonstrated the importance of considering sex and genetic interactions in studies of disease predisposition and complex traits.",
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AU - Suen, Eddie W C

AU - Chan, Iris H S

AU - Orwoll, Eric

AU - Ho, Suzanne C.

AU - Chan, Frank W K

AU - Kwok, Anthony W L

AU - Kwok, Timothy

AU - Woo, Jean

AU - Leung, Ping Chung

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N2 - Background: Osteoporosis is a common condition among elderly. Genetic mapping studies repeatedly located the distal short arms of X-chromosome as the quantitative trait loci (QTL) for BMD in mice. Fine mapping of a syntenic segment on Xp22 in a Caucasian female population suggested a moderate association between lumbar spine (LS) BMD and 2 intronic SNPs in the Pirin (PIR) gene, which encodes an iron-binding nuclear protein. This study aimed to examine genetic variations in the PIR gene by a comprehensive tagging method and its sex-specific effects on BMD and osteoporotic risk. Methods: Two thousand men and 2000 women aged 65 or above were recruited from the community. BMDs at the LS, femoral neck, total hip and whole body were measured and followed up at 4-year. Genotyping was performed for tagSNPs of PIR gene including adjacent regions, and the PIR haplotypes were inferred using PHASE program. Results: Analysis by linear regression showed a significant association between SNP rs5935970 and LS-BMD, while haplotype T-T-A was significantly associated with BMD of all measured sites. However, none of such associations were found in men. Linear Mixed Model also confirmed the same sex-specific and site-specific effect for longitudinal BMD changes. Conclusion: In addition to confirming the association between BMDs and the PIR gene, we also revealed that this finding is sex-specific, possibly due to an X-linked effect. This study demonstrated the importance of considering sex and genetic interactions in studies of disease predisposition and complex traits.

AB - Background: Osteoporosis is a common condition among elderly. Genetic mapping studies repeatedly located the distal short arms of X-chromosome as the quantitative trait loci (QTL) for BMD in mice. Fine mapping of a syntenic segment on Xp22 in a Caucasian female population suggested a moderate association between lumbar spine (LS) BMD and 2 intronic SNPs in the Pirin (PIR) gene, which encodes an iron-binding nuclear protein. This study aimed to examine genetic variations in the PIR gene by a comprehensive tagging method and its sex-specific effects on BMD and osteoporotic risk. Methods: Two thousand men and 2000 women aged 65 or above were recruited from the community. BMDs at the LS, femoral neck, total hip and whole body were measured and followed up at 4-year. Genotyping was performed for tagSNPs of PIR gene including adjacent regions, and the PIR haplotypes were inferred using PHASE program. Results: Analysis by linear regression showed a significant association between SNP rs5935970 and LS-BMD, while haplotype T-T-A was significantly associated with BMD of all measured sites. However, none of such associations were found in men. Linear Mixed Model also confirmed the same sex-specific and site-specific effect for longitudinal BMD changes. Conclusion: In addition to confirming the association between BMDs and the PIR gene, we also revealed that this finding is sex-specific, possibly due to an X-linked effect. This study demonstrated the importance of considering sex and genetic interactions in studies of disease predisposition and complex traits.

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